Improvement In Mucociliary Clearance Research Articles

Оториноларингологическая помощь детям с хроническим риносинуситом

Chronic rhinosinusitis (CRS) is a common disease that has a significant impact on the health and life quality of children. CRS occurs when the disease lasts for more than 12 weeks and it can lead to serious complications. Specialized ENT care is crucial for the diagnosis, treatment and rehabilitation of patients with CRS. This review presents the system of providing specialized ENT care to children in Russia, as well as the organization of medical and social support for children with CRS. Special attention is paid to the prevention of CRS exacerbations in children, including the prevention and timely treatment of acute and recurrent respiratory viral infections, reduction of bacterial load, improvement of mucociliary clearance and follow-up. It is also noted that the formation of a Health School for children with CRS will help teach children to recognize the signs of CRS exacerbations and take action at the first deterioration signs. KEYWORDS: specialized ENT care, chronic rhinosinusitis in children, Health School, medical and social support for children, respiratory viral infection FOR CITATION: Dvornikova T.A., Alexandrova O.Yu. ENT care for children with chronic rhinosinusitis. Russian Medical Inquiry. 2024;8(8):499–504 (in Russ.). DOI: 10.32364/2587-6821-2024-8-8-9.

Bronchiectasis: an update for the general practitioner.

Bronchiectasis is a heterogeneous lung condition characterized by irreversible bronchial dilatation, chronic inflammation and frequent exacerbations. Diagnosis is based on the presence of a productive cough most of the days, a history of exacerbations and the presence of bronchial dilatation on chest CT scan. Etiologic and microbiologic workup should be performed to determine the underlying cause. A personalized treatment approach is mandatory and includes patient education, improvement of mucociliary clearance, prevention and treatment of exacerbations, in order to preserve lung function and improve quality of life.

Airway Clearance and Mucoactive Therapies.

The respiratory system is constantly exposed to external pathogens but has different and effective defense systems. The pathophysiology of bronchiectasis affects the defense system considerably in that alterations occur in the airway that reduce its effectiveness in mucociliary clearance and the greater presence of mucins leads to the accumulation of more adherent and viscous mucus. One of the pillars of treatment of this disease should be improvement of mucociliary clearance and a decrease in the adherence and viscosity of the mucus. To this end, the mobilization of secretions must be increased through effective respiratory physiotherapy techniques, which can be manual and/or instrumental. The properties of mucus can be modified to improve its mobilization through the use of a mucoactive agent. Despite the increase in the number and quality of studies, the evidence for these treatments remains scarce, although their application is recommended in all guidelines.

Effect of lumacaftor-ivacaftor on mucociliary clearance and clinical outcomes in cystic fibrosis: Results from the PROSPECT MCC sub-study

CFTR function is required for normal mucociliary clearance (MCC) and cough-assisted clearance (CC). Lumacaftor-ivacaftor is approved for use in people with cystic fibrosis (CF) carrying two copies of F508del-CFTR. In this observational study performed at four study sites, we characterized the effect of lumacaftor-ivacaftor on mucociliary and cough clearance and related this to other clinical and research endpoints after one month of treatment. Twenty-five adolescents and adults were enrolled. No effect on whole lung MCC was observed, but CC was significantly increased. Sweat chloride improved by 18 mEq/L in this group, indicating a modest restoration of CFTR activity, but no demonstrable change in FEV1 or lung clearance index was observed. We speculate that the modest effect of lumacaftor-ivacaftor on CFTR function was insufficient to yield an improvement in MCC.

Comparison of Hypertonic Saline with Normal Saline in Nasal Irrigation Post Endoscopic Sinus Surgery.

Functional endoscopic sinus surgery (FESS) is indicated for the treatment of chronic rhinosinusitis that is refractory to medical treatment. Nasal irrigation is a classic and powerful adjunctive method for the management of chronic rhinosinusitis after FESS [5]. This study aimed to compare the effects of hypertonic saline and isotonic saline nasal irrigation following endoscopic sinus surgery. The study was conducted in the Department of Otorhinolaryngology at Mahatma Gandhi Medical College and Hospital, Jaipur, India, on 156 patients, who had chronic rhinosinusitis with or without nasal polyposis, and were resistant to conservative management. All patients underwent functional endoscopic sinus surgery. Patients were advised to perform nasal douching post-surgery, and were randomly divided into two groups based on the douching solution they used. Group 1 was given hypertonic saline (3%) while Group 2 was given isotonic saline (0.9%). Patients were examined at weeks 1, 3 and 6 post-operatively. Outcomes of irrigation using both solutions were assessed by- 20-item Sino-Nasal Outcome Test (SNOT20) scores [13], Visual analogue scale (VAS) scores [1, 2], mucociliary clearance (MCC) assessment [14] and endoscopic examination. The group receiving hypertonic saline showed significant improvement in 20-item Sino-Nasal Outcome Test scores, Visual analogue scale scores and improvement of sino-nasal mucosa from polypoidal to cobblestone, in the follow up period. However improvement in mucociliary clearance and resolution of postoperative crustings was consistent in both groups. Hypertonic saline nasal irrigation post FESS brings greater benefits on symptom improvement and normalization of the sino-nasal mucosa over isotonic saline.

A four week trial of hypertonic saline in children with mild cystic fibrosis lung disease: Effect on mucociliary clearance and clinical outcomes

BackgroundHypertonic saline (HS) is commonly prescribed for children with cystic fibrosis (CF) despite the absence of strong data indicating clinical efficacy in a population with mild lung disease. We hypothesized that HS treatment would result in a sustained improvement in mucociliary clearance (MCC) in children with CF who had minimal lung disease, thus providing evidence for a biologically relevant effect that also may be associated with clinical improvements. MethodsWe performed a randomized, placebo controlled, double blind study of 6% versus 0.12% sodium chloride, delivered three-times daily with an eFlow nebulizer for 4 weeks. MCC was measured using gamma scintigraphy at baseline, 2-hours after the first study treatment, and ~12-hours after the final dose (at day 28). Spirometry, respiratory symptoms (CFQ-R), and safety were also assessed. ResultsStudy treatments were generally well tolerated and safe. HS (6% sodium chloride) resulted in a significant, sustained improvement from baseline in whole lung clearance after 4 weeks of therapy (p = 0.014), despite absence of a prolonged single-dose effect after the initial dose. This sustained change (12 hrs after prior dose) was significantly greater when compared to placebo (0.12% sodium chloride) treatment (p = 0.016). Improvements in spirometry with HS did not reach statistical significance but correlated with MCC changes. ConclusionsThe observed sustained improvement in MCC with HS suggests that this treatment may yield health benefits, even in relatively mildly affected children with CF. Highlighting this physiologic finding is important due to the lack of meaningful, validated endpoints in this population.

Zinc and respiratory tract infections: Perspectives for COVID‑19 (Review).

In view of the emerging COVID-19 pandemic caused by SARS-CoV-2 virus, the search for potential protective and therapeutic antiviral strategies is of particular and urgent interest. Zinc is known to modulate antiviral and antibacterial immunity and regulate inflammatory response. Despite the lack of clinical data, certain indications suggest that modulation of zinc status may be beneficial in COVID-19. In vitro experiments demonstrate that Zn2+ possesses antiviral activity through inhibition of SARS-CoV RNA polymerase. This effect may underlie therapeutic efficiency of chloroquine known to act as zinc ionophore. Indirect evidence also indicates that Zn2+ may decrease the activity of angiotensin-converting enzyme 2 (ACE2), known to be the receptor for SARS-CoV-2. Improved antiviral immunity by zinc may also occur through up-regulation of interferon α production and increasing its antiviral activity. Zinc possesses anti-inflammatory activity by inhibiting NF-κB signaling and modulation of regulatory T-cell functions that may limit the cytokine storm in COVID-19. Improved Zn status may also reduce the risk of bacterial co-infection by improving mucociliary clearance and barrier function of the respiratory epithelium, as well as direct antibacterial effects against S. pneumoniae. Zinc status is also tightly associated with risk factors for severe COVID-19 including ageing, immune deficiency, obesity, diabetes, and atherosclerosis, since these are known risk groups for zinc deficiency. Therefore, Zn may possess protective effect as preventive and adjuvant therapy of COVID-19 through reducing inflammation, improvement of mucociliary clearance, prevention of ventilator-induced lung injury, modulation of antiviral and antibacterial immunity. However, further clinical and experimental studies are required.

Duration of action of hypertonic saline on mucociliary clearance in the normal lung.

Inhalation of hypertonic saline (HS) acutely enhances mucociliary clearance (MC) in both health and disease. In patients with cystic fibrosis (CF), repeated use of HS causes a sustained improvement in MC as well as clinical benefit. The pharmacodynamic duration of activity on MC may be an important determinant of its therapeutic potential in other airways diseases. Before moving toward testing the clinical benefits of HS for non-CF indications, we sought to assess the duration of pharmacodynamic effects of HS in healthy subjects by performing radiotracer clearance studies at baseline, 30-min post-HS administration, and 4-h post-HS administration. Indeed, acceleration of MC was observed when measured 30 min after HS inhalation. This acceleration was most pronounced in the first 30 min after inhaling the radiotracer in the central lung region (mean Ave30Clr = 15.5 vs. 8.6% for 30-min post-HS treatment vs. mean baseline, respectively, P < 0.005), suggesting that acute HS effects were greatest in the larger bronchial airways. In contrast, when MC was measured 4 h after HS administration, all indices of central lung region MC were slower than at baseline: Ave30Clr = 5.9% vs. 8.6% (P = 0.10); Ave90Clr = 12.4% vs. 16.8% (P < 0.05); clearance through 3 h = 29.4 vs. 43.7% (P < 0.002); and clearance through 6 h = 39.4 vs. 50.2% (P < 0.02). This apparent slowing of MC in healthy subjects 4-h post-HS administration may reflect depletion of airway mucus following acute HS administration.

A Double-Blind Randomized Controlled Trial of Normal Saline, Lactated Ringer's, and Hypertonic Saline Nasal Irrigation Solution after Endoscopic Sinus Surgery

Nasal douching is commonly performed after endoscopic sinus surgery (ESS). There is a lack of studies comparing the clinical effect of various douching solutions after ESS. This study investigated the clinical effects of normal saline, lactated Ringer's, and hypertonic saline nasal douching solutions after ESS. Adult patients (41.8 ± 12.9 years) undergoing bilateral ESS for chronic rhinosinusitis at a single tertiary referral center were blindly randomized to one of the three study solutions and reviewed on postoperative weeks 1, 3, and 6. The 20-item Sino-Nasal Outcome Test (SNOT-20) scores, visual analog scale (VAS) symptom scores, digital video capture of the sinus cavities, and mucociliary clearance (MCC) times were performed at each visit. The mucosa appearances were scored by a second investigator, blinded to the douching solution. Seventy-four patients were recruited. All groups showed an improvement with treatment in SNOT-20 scores and VAS scores, as well as endoscopic evaluation of mucosa appearance over time. There was no improvement of MCC during the treatment period. Irrigation with lactated Ringer's solution resulted in better symptom scores in SNOT-20 (p < 0.05) and VAS (p < 0.05), compared with irrigation with normal saline or hypertonic saline solutions. Patients receiving hypertonic saline solutions had less polypoidal mucosa at week 6. Douching with lactated Ringer's solution after ESS results in better improvement in sinonasal symptoms, compared with normal saline or hypertonic saline solutions.

Acute Hyperkalemia Associated with Inhalation of a Potent ENaC Antagonist: Phase 1 Trial of GS-9411

Inhaled epithelial sodium channel (ENaC) blockers are designed to increase airway surface liquid volume, thereby benefiting cystic fibrosis patients. This study evaluated the safety, tolerability, and pharmacokinetics of multiple doses of ENaC blocker GS-9411, in healthy participants. This randomized, double-blind, placebo-controlled, parallel-group, residential, Phase 1 study evaluated inhaled GS-9411 (2.4, 4.8, and 9.6 mg) or placebo, dosed twice daily for 14 days. GS-9411 was well tolerated; 86.1% of treated participants completed dosing (n=31/36). Cough and dizziness (27.8% participants each; most of mild severity) were the most commonly reported adverse events and occurred in both placebo and GS-9411 treatment groups. Arrhythmias were not observed for GS-9411-treated participants, and electrocardiographic changes were not considered clinically significant. Serum potassium levels exceeded the upper limit of normal (>5 mmol/L), 4 hr after the morning dose in GS-9411 (n=16/24) and placebo (n=4/12) treatment groups (38 incidences total). Retesting revealed levels had returned to normal within 2-3 hr. In urine electrolyte analyses, obtained 0-6 hr after the Day 1 morning dose, mean sodium/potassium ratios significantly increased from values 0-6 hr before dosing. Increased urine sodium/potassium ratios corresponded with high urine concentrations of active GS-9411 metabolites, which inhibited sodium reabsorption in the kidney, leading to the observed transient hyperkalemia in these participants. Inhaled GS-9411 was well tolerated except for the emergence of transient clinically significant hyperkalemia; this finding resulted in termination of further clinical development of this drug and will necessitate development of a new generation of ENaC blockers, which provide a sustained improvement in mucociliary clearance, while reducing renal exposure to ENaC blockade. Transient increases in mean urine sodium/potassium ratios appeared to be the first signal of electrolyte imbalances resulting from drug-induced block of ENaC in the kidney. The results of this study strongly suggest that clinical trials of novel ENaC blockers will require intensive measurement of plasma and urine electrolyte levels.

Acute inhalation of hypertonic saline does not improve mucociliary clearance in all children with cystic fibrosis

BackgroundLittle is known of how mucociliary clearance (MCC) in children with cystic fibrosis (CF) and normal pulmonary function compares with healthy adults, or how an acute inhalation of 7% hypertonic saline (HS) aerosol affects MCC in these same children.MethodsWe compared MCC in 12 children with CF and normal pulmonary function after an acute inhalation of 0.12% saline (placebo), or HS, admixed with the radioisotope 99 mtechnetium sulfur colloid in a double-blind, randomized, cross-over study. Mucociliary clearance on the placebo day in the children was also compared to MCC in 10 healthy, non-CF adults. Mucociliary clearance was quantified over a 90 min period, using gamma scintigraphy, and is reported as MCC at 60 min (MCC60) and 90 min (MCC90).ResultsMedian [interquartile range] MCC60 and MCC90 in the children on the placebo visit were 15.4 [12.4-24.5]% and 19.3 [17.3-27.8%]%, respectively, which were similar to the adults with 17.8 [6.4-28.7]% and 29.6 [16.1-43.5]%, respectively. There was no significant improvement in MCC60 (2.2 [-6.2-11.8]%) or MCC90 (2.3 [-1.2-10.5]%) with HS, compared to placebo. In addition, 5/12 and 4/12 of the children showed a decrease in MCC60 and MCC90, respectively, after inhalation of HS. A post hoc subgroup analysis of the change in MCC90 after HS showed a significantly greater improvement in MCC in children with lower placebo MCC90 compared to those with higher placebo MCC90 (p = 0.045).ConclusionsThese data suggest that percent MCC varies significantly between children with CF lung disease and normal pulmonary functions, with some children demonstrating MCC values within the normal range and others showing MCC values that are below normal values. In addition, although MCC did not improve in all children after inhalation of HS, improvement did occur in children with relatively low MCC values after placebo. This finding suggests that acute inhalation of hypertonic saline may benefit a subset of children with low MCC values.Trial RegistrationClinicalTrials.gov: NCT01293084

Reversibility of impaired nasal mucociliary clearance in smokers following a smoking cessation programme

Smoking cessation (SC) is recognized as reducing tobacco-associated mortality and morbidity. The effect of SC on nasal mucociliary clearance (MC) in smokers was evaluated during a 180-day period. Thirty-three current smokers enrolled in a SC intervention programme were evaluated after they had stopped smoking. Smoking history, Fagerström's test, lung function, exhaled carbon monoxide (eCO), carboxyhaemoglobin (COHb) and nasal MC as assessed by the saccharin transit time (STT) test were evaluated. All parameters were also measured at baseline in 33 matched non-smokers. Smokers (mean age 49 ± 12 years, mean pack-year index 44 ± 25) were enrolled in a SC intervention and 27% (n = 9) abstained for 180 days, 30% (n = 11) for 120 days, 49.5% (n = 15) for 90 days or 60 days, 62.7% (n = 19) for 30 days and 75.9% (n = 23) for 15 days. A moderate degree of nicotine dependence, higher education levels and less use of bupropion were associated with the capacity to stop smoking (P < 0.05). The STT was prolonged in smokers compared with non-smokers (P = 0.002) and dysfunction of MC was present at baseline both in smokers who had abstained and those who had not abstained for 180 days. eCO and COHb were also significantly increased in smokers compared with non-smokers. STT values decreased to within the normal range on day 15 after SC (P < 0.01), and remained in the normal range until the end of the study period. Similarly, eCO values were reduced from the seventh day after SC. A SC programme contributed to improvement in MC among smokers from the 15th day after cessation of smoking, and these beneficial effects persisted for 180 days.

Erdosteine: Antitussive and Anti-inflammatory Effects

Erdosteine is a multifactorial drug currently used in COPD for its rheologic activity on bronchial secretions and its positive effects on bacterial adhesiveness. Erdosteine produces an active metabolite (Met 1) which was shown to produce antioxidant effects during the respiratory burst of human PMNs, due to the presence of an SH group. The substantial antitussive effects of erdosteine were first documented in clinical trials even though mucolytic agents are regarded as not consistently effective in ameliorating cough in patients with bronchitis, although they may be of benefit to this population in other ways. Actually, a mucolytic drug could exert antitussive effects if it also affects mucus consistency and enhances ciliary function. In the last decade, data from several studies on animal models pointed to the possible antitussive and anti-inflammatory properties of erdosteine and an indirect anti-inflammatory mechanism of action was suggested. Recently, data from some controlled versus placebo studies documented the antioxidant properties of erdosteine in humans and in current smokers with COPD. The mechanism of action was described as related to erdosteine's ability to inhibit some inflammatory mediators and some pro-inflammatory cytokines that are specifically involved in oxidative stress. As oxidative stress is also presumed to impair beta-adrenoceptor function and contribute to airway obstruction, specific controlled studies recently investigated the effect of antioxidant intervention on short-term airway response to salbutamol in nonreversible COPD, according to a double-blind design versus placebo and NAC. Only erdosteine consistently restored a significant short-term reversibility in COPD subjects, previously unresponsive to beta(2) adrenergics. This peculiar activity of erdosteine (to our knowledge never previously assessed) proved related to the ROS scavenging activity (which actually proved equal to that of N), and its significant inhibiting effect on lipoperoxidation (8-isoprostane) proved discriminant between treatments, with antioxidant and anti-inflammatory effects the main determinants of the erdosteine multifactorial properties. In addition, antitussive effects may be regarded as related to its anti-inflammatory properties via the improvement of mucociliary clearance and the reduction of chemokines from epithelial cells. Finally, a sort of "sensitization" of 2-adrenoceptors can also be speculated due to the same mechanisms of action; if confirmed by further controlled studies, this particular property would suggest a novel therapeutic role of erdosteine in COPD.

Hypertonic saline inhibits luminal sodium channels in respiratory epithelium

Physical exercise with increased ventilation leads to a considerable rise in water loss from the airways. The mechanisms underlying the regulation of transepithelial fluid transport necessary to compensate for these losses are unknown but may include changes in luminal ion channel conductance. The present study was designed to examine the effects of an increase in luminal chloride and sodium concentrations which may locally occur during hyperventilation on luminal ion conductance in the respiratory epithelium of healthy controls and patients diagnosed with cystic fibrosis (CF). Changes in luminal chloride and sodium conductance were inferred by recording nasal potential difference in eight healthy subjects and 10 patients with CF, using superfusing solutions based on isotonic saline (150 mM) on one occasion and solutions based on hypertonic saline (300 mM) on the other. Switching from isotonic to hypertonic saline superfusion decreased potential difference in controls and CF patients significantly. Amiloride induced a decrease of potential difference which was larger with isotonic than with hypertonic saline (controls 9.5 +/- 6.1 vs. 3.7 +/- 4.6 mV; CF 17.2 +/- 7.2 vs. 9.8 +/- 7.6 mV). Chloride conductance stimulated with solutions low in chloride and containing isoproterenol was not significantly changed by hypertonic saline solutions compared with isotonic solutions in both groups. The findings indicate a significant inhibition of luminal sodium conductance by high luminal sodium concentrations. This mechanism may be involved in the regulation of fluid transport across the respiratory epithelium during exercise and in the improvement of mucociliary clearance and lung functions with inhalation of hypertonic saline in CF.

Steroid Effects on Mucociliary Clearance in Outpatient Asthma

Asthma, a chronic inflammatory condition of airways, responds to therapy with anti-inflammatory medications, for example, inhaled (ICS) and/or systemic (SS) corticosteroids. It is associated with impaired clearance of airway secretions. We studied effects of ICS and SS on mucociliary clearance (MC) in outpatient asthma through an in vivo, randomized, placebo-controlled single blind study with patients acting as their own control. Using a gamma camera and radiolabeled aerosol, we measured MC at baseline, after 4 days of nebulized treatment and after 5 days of oral prednisone. MC was expressed as percent of retained activity over time. Spirometry was performed before each MC study. Treatment with nebulized budesonide did not affect MC or forced expiratory volume at 1 sec (FEV1). Treatment with SS was associated with a significant improvement in MC at 24 h (baseline, 41 +/- 6; post-SS, 36 +/- 5; p = 0.04). Post hoc analysis revealed that MC changed only in those patients with significant changes in deposition (specific Central-to-Peripheral ratio C/P--baseline, 1.57 +/- 0.16; post-SS, 1.73 +/- 0.21; n = 6; p = 0.05), suggesting that the changes in MC were not directly related to therapy. In outpatient asthma, MC is unaffected by 4-5 days of anti-inflammatory therapy in spite of significant changes in FEV1.

Reducing airways inflammation to prevent exacerbations in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is amajor cause of handicap, mortality and health careexpenses (1). Altered quality of life (QOL) is a hallmarkof the disease, and relates mainly to dyspnoea andexacerbations: both QOL at steady-state and its rate ofdecline over time correlate to the frequency of acuterespiratory events (2, 3). In parallel, hospitalizations forexacerbations in the most severe patients are importantdeterminants of health care costs (4). Thus, preventingexacerbations is a major goal of care for COPD patients,both from an individual and collective point of view.Inflammation and COPD exacerbationsIn most cases, COPD occurs in smokers and ex-smokers,in whom airflow limitation is the consequence of variousdegrees of emphysema, chronic bronchiolitis and mucusplugging (5). These components of the disease have beenlinked to inflammatory and remodelling processes in theairways and lung parenchyma, involved inflammatorycells being mainly neutrophils, B and T lymphocytes andmacrophages (5, 6). Airways inflammation is moreintense during exacerbations, as shown by increases inthe levels of (i) expression of neutrophil elastase, CXCL-5, CXCL-8 and CXCR1/2 in biopsies (7), (ii) exhaledLTB4 and 8-isoprostane in breath condensates (8), (iii)interleukin (IL)-8 and tumour necrosis factor (TNF)-a insputum (9).Infections are a leading cause of exacerbations andfurther amplify airway inflammation (10). However,about one half of exacerbations occur in the absence ofany detectable infective pathogen, which may not preventinflammation from increasing (11). Besides, higher levelsof inflammatory markers in the airways of patients atsteady-state are also associated with more frequentexacerbations (12). Studies of the East London COPDcohort even suggest the existence of a particular subgroupof COPD patients called frequent exacerbators, whoconsistently have more than 2–3 exacerbations per year(13). In these patients, QOL is more altered, forcedexpiratory volume at 1 s (FEV

慢性副鼻腔炎鼻汁の成因と対策

Nasal mucus hypersecretion is a feature of chronic sinusitis (CS). Bacterial infection, which initiates neutrophil accumulation in the nose and sinuses is an initial cause of CS. The specific neutrophil products to stimulate mucus glycoprotein (MGP) secretion are neutrophil elastase, cathepsin G and platelet-activating factor. Eicoanoids are a group of lipids derived from arachidonic acid that is released from the cell membranes of inflammatory and epithelial cells, and also contribute to MGP production. Bacterial products, such as lipopolysaccharide and elastase from some bacteria, are potent secretagogues. Such products derived from inflammatory cells and bacterias are retained in sinuses for a long time because of obstruction of the sinus ostium and mucociliary dysfunction of the nose and sinuses. Submucosal gland cells are hyperplastic and hypertrophic but goblet cells are not, and the major source of MGP hypersecretion is submucosal gland cells rather than goblet cells. The role of neural innervation of submucosal glands on MGP overproduction has not yet to be elucidated.The rheologic properties of nasal mucus from CS patients are much higher than the optimal viscoelasticity for mucociliary transport. Since MGP mainly determines the high viscosity and the high elasticity of nasal mucus, a control of MGP production could contribute to the normalization of abnormal viscoelasticity, and result in the improvement of mucociliary clearance. This is accomplished by removing the sinus retention that contains many secretagogues. Although current pharmacological approaches to airway mucus production are limited, glucocorticoid appears to be the most effective among the few useful drugs. The effect of 14-membered macrolide antibiotics on MGP production is still controversial. Some mucolytic agents change the conformations of MGP and lead to the reduction of viscoelasticity when they are administered topically or systemically.The mechanisms of nasal mucus hypersecretion are also discussed in relation to the etiology of CS.

Effect of a Thromboxane A2 Antagonist on Sputum Production and Its Physicochemical Properties in Patients With Mild to Moderate Asthma

To determine the effects of a specific thromboxane A(2) (TxA(2)) receptor antagonist, seratrodast, on asthma control and airway secretions. Multicenter, double-blind, randomized, placebo-controlled study. Forty-five patients with mild to moderate asthma who had been continuously expectorating sputum of > 20 g/d. Patients with a current pulmonary infection or taking oral corticosteroids, antibiotics, or mucolytic agents were excluded from the trial. Following a 2-week run-in period, while pulmonary function, sputum production, and mucociliary function were assessed, patients were assigned to receive seratrodast, 40 mg/d, or placebo for 6 weeks. During the treatment period, the changes in FEV(1) and peak expiratory flow (PEF) were not different between the two patient groups, but there were significant reductions in diurnal variation of PEF (p = 0.034), frequency of daytime asthma symptoms (p = 0.030), and daytime supplemental use of beta(2)-agonist (p = 0.032) in the seratrodast group. For sputum analysis, seratrodast treatment decreased the amount of sputum (p = 0.005), dynamic viscosity (p = 0. 007), and albumin concentration (p = 0.028), whereas it had no effect on elastic modulus or fucose concentration. Nasal clearance time of a saccharin particle was shortened in the seratrodast group at week 4 (p = 0.031) and week 6 (p = 0.025), compared with the placebo group. Blockade of TxA(2) receptor has minimal effects on pulmonary function, but may cause an improvement in mucociliary clearance by decreasing the viscosity of airway secretions.

Effect of increasing doses of hypertonic saline on mucociliary clearance in patients with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis are known to have decreased mucociliary clearance. It has previously been shown that inhalation of a 7.0% solution of hypertonic saline significantly improved mucociliary clearance...

Reduced Effect of Inhaled β2-Adrenergic Agonists on Lung Mucociliary Clearance in Patients With Cystic Fibrosis

It has been suggested that the defective cyclic AMP-dependent Cl- secretion and the increased Na+ absorption from airway epithelia in cystic fibrosis (CF) may lead to dehydrated secretions and impaired mucociliary clearance. Beta 2-adrenergic agonists are unable to stimulate the Cl- transport in the airways in CF while being able to do so in normal airways. Thus, we questioned whether the beta 2-adrenergic agonist, terbutaline, would improve mucociliary clearance in patients with CF as it does in healthy subjects. A double-blind, randomized cross-over trial. Whole lung and regional mucociliary clearance of a radioaerosol was measured for 3 h by gamma camera. One minute of cough clearance was measured at 3 h. Pulmonary function was measured before and after the gamma camera study. Ten young patients with CF were studied; three were heterozygous for deletion of the phenylalanine at position 508 (delta F508), and seven were delta F508 homozygous. Inhalation of 1 mg of terbutaline (4 puffs) and placebo via a metered-dose inhaler by spacer. The largest differences in tracheobronchial retention (percent) in the whole lung and regional lung zones were generally observed within 1 h after terbutaline and placebo treatment: whole lung (mean +/- SD), 60 +/- 22 percent and 63 +/- 20 percent; central zone, 41 +/- 19 percent and 50 +/- 25 percent; midzones, 65 +/- 27 percent and 63 +/- 19 percent; and peripheral zones, 77 +/- 28 percent and 72 +/- 28 percent, respectively [p > 0.1]. Whereas none of these differences was statistically significant, subanalyses suggested an improvement in mucociliary clearance by terbutaline in the three delta F508 heterozygous patients but not in the seven delta F508 homozygous patients. One minute of voluntary coughing resulted in clearance of less than 8 percent of the initial radioactivity, with a trend of more peripheral zone clearance after terbutaline compared with placebo. A small significant decrease in airway resistance was detected 3 h after terbutaline. We conclude that 1 mg of terbutaline did not improve mucociliary clearance significantly in the patients with CF. Also, the effect of terbutaline was much less than demonstrated earlier in healthy subjects. This is consistent with earlier findings of a lack of beta-adrenergic modulation of Cl- transport in CF. Thus, no rehydration of the dry mucus in CF is expected, and a possible beta 2-agonist-induced increase in ciliary beating would have only a minor effect on overall mucociliary clearance.